Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Neuropathol Exp Neurol. 2008 Aug;67(8):803-18. doi: 10.1097/NEN.0b013e3181815994.

Temporal neuropathologic and behavioral phenotype of 6neo/6neo Pompe disease mice.

Author information

  • 1Department of Neurology (RLS), Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. richard_sidman@hms.harvard.edu

Abstract

Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene. The most common form is rapidly progressive with glycogen storage, particularly in muscle, which leads to profound weakness, cardiac failure, and death by the age of 2 years. Although usually considered a muscle disease, glycogen storage also occurs in the CNS. We evaluated the progression of neuropathologic and behavioral abnormalities in a Pompe disease mouse model (6neo/6neo) that displays many features of the human disease. Homozygous mutant mice store excess glycogen within large neurons of hindbrain, spinal cord, and sensory ganglia by the age of 1 month; accumulations then spread progressively within many CNS cell types. "Silver degeneration" and Fluoro-Jade C stains revealed severe degeneration in axon terminals of primary sensory neurons at 3 to 9 months. These abnormalities were accompanied by progressive behavioral impairment on rotorod, wire hanging, and foot fault tests. The extensive neuropathologic alterations in this model suggest that therapy of skeletal and cardiac muscle disorders by systemic enzyme replacement therapy may not be sufficient to reverse functional deficits due to CNS glycogen storage, particularly early-onset, rapidly progressive disease. A better understanding of the basis for clinical manifestations is needed to correlate CNS pathology with Pompe disease manifestations.

PMID:
18648322
[PubMed - indexed for MEDLINE]
PMCID:
PMC2743262
Free PMC Article

Images from this publication.See all images (13)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Lippincott Williams & Wilkins Icon for PubMed Central
    Loading ...
    Write to the Help Desk